Biomedical subjects
Publications and source records attributed to M Joshi.
A case is described of fulminant meningococcal meningitis occurring 1 day after serious head and facial trauma. Although meningococcus is one of the most common causes of bacterial meningitis in general, it is distinctly rare as a cause of posttraumatic meningitis. A review of the literature is included.
An in vitro assay for the simultaneous measurement of lipid peroxidation (LPO) and bilirubin degradation (BRD) activities in rat liver microsomes has been developed; a good correlation between the 2 activities was observed (r = 0.78). In the Gunn rat a lipid free diet caused an increase in plasma bilirubin (62.4 +/- 25.8%, n = 6) and a concomitant decrease in both hepatic microsomal LPO and BRD to zero. In contrast, on a 25% lipid diet there was a decrease in plasma bilirubin (46.1 +/- 3.6%; n = 8) associated with an increase in LPO (1.26 +/- 0.11 nmol/min/mg protein, and BRD (0.21 +/- 0.6 nmol/min/mg protein). Therefore, in the absence of bilirubin glucuronidation, dietary modulation of plasma bilirubin and lipid peroxidation appear to be closely associated.
New understanding in the pathogenesis of adrenoneuropathy (ANP), formerly called adrenoleukodystrophy (ALD) and adrenomyeloneuropathy (AML), has led to greater awareness of the disease with resultant increase in the number of new cases being diagnosed. We report adrenoneuropathy in two siblings, one of whom had associated affective symptoms and died undiagnosed in prison. The other sibling died at the age of eight with severe cerebral demyelination. Affective symptoms have been described in ANP, but the association of Hashimoto's thyroiditis and accelerated atherosclerosis in this case is unique. We would like to stress the characteristic gross appearance of the adrenals in ANP that may help in identifying undiagnosed cases of adrenoneuropathy in surgical and autopsy specimens. Genetic counseling and family-pedigree analysis with diet restriction and diet therapy will be invaluable in such cases.
We report a case of juvenile nutritional megaloblastic anemia with emphasis on the histologic findings in the upper gastrointestinal system, including the previously unreported feature of periodic acid-Schiff (PAS)-negative, Alcian blue-negative cytoplasmic vacuoles (CV) in duodenal enterocytes. These CV were reminiscent of those described in abetalipoproteinemia; however, the patient's lipid profile was normal. All histopathologic changes in the upper gastrointestinal tract (with the exception of mild reflux esophagitis) reverted to normal following parenteral administration of vitamin B12. This case supports the notion that CV in enterocytes are a component (albeit a rare one) of the histopathology in cobalamin deficiency.
The relationship between blunt abdominal trauma and intra-abdominal abscess (IAA) is discussed infrequently; therefore we conducted a retrospective review of 4050 multiple blunt trauma admissions from January 1986 to July 1988. Of 325 patients who had a laparotomy for blunt abdominal trauma, we identified 15 (4.6%) who had 40 IAAs. The most common intra-abdominal injuries involved the spleen and liver. Splenectomy increased the risk for IAA in contrast to splenic salvage. Blunt injuries to the kidney and pancreas, when occurring in multiple trauma patients, carried a significant risk of IAA. Associated multiple extra-abdominal injuries and high transfusion requirements increased the risk for IAA formation. Most of the IAAs were located in the upper quadrants. There was a 46% incidence of multiple IAA, which in turn had an 80% chance of recurrence after initial drainage. Enterobacter species played an important role in the formation of IAA in our trauma patients. Three patients (20%) died. Poor prognostic indicators included a high injury severity score, high transfusion requirements, the presence of pelvic fracture, positive blood cultures, multiple organisms per abscess, and multiple-organ system failure.
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Heart Reactive Antibodies (HRA) of IgG and IgM classes were investigated in 79 patients in four clinically classified groups. Group I comprised of 16 children with Acute Rheumatic Fever (ARF) and Group II consisted of 15 cases with active Rheumatic Heart Disease (RHD). Twenty seven cases of ARF and RHD in remission and 21 adults with quiescent RHD were included in Groups III and IV respectively. Control groups comprised of 14 normal, healthy, donors and eight Post Streptococcal Acute Glomerular Nephritis (PSAGN) cases. Low levels of HRA of IgG and IgM classes were detected in control groups. The overall incidence of HRA of IgG and IgM classes was 82.28 and 39.24% respectively in the patient group. An increased frequency of HRA-IgM antibodies was observed in Groups I, III and IV (p less than 0.01, 0.001 and 0.025 respectively). All the four groups demonstrated a highly significant increase in incidence of HRA--IgG class (p less than 0.0005). Persistence of high titres of HRA-IgG class in ARF and RHD is reported in the paper.
A new assay technique for the determination of neurotransmitter binding in retinal fragments has been used to characterize and quantify beta-adrenergic receptors with the ligand [3H]CGP-12177. This assay allowed us to quantify beta-adrenergic receptors in the retina, pineal gland, and hypothalamus obtained from individual rats during a 10-hr period around the switch from light to dark under a 12-hr light/12-hr dark lighting cycle. A significant rhythm of beta-adrenergic binding was observed in the retina and pineal gland. These rhythms were abolished by chronic lithium treatment. In contrast to previous observations in whole brain preparations, lithium did not affect beta-adrenergic binding in brain tissue (hypothalamus) using this assay. Our data suggest that lithium may attenuate beta-adrenergic receptor down-regulation in pineal and retinal tissue. To the extent that this mechanism is important for the coding of information about light and dark in the environment, these observations might assist in our understanding of the clinical chronopharmacological properties reported for lithium.
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Ceftazidime is a new antimicrobial agent possessing excellent in vitro activity against most members of the family Enterobacteriaceae and against Pseudomonas aeruginosa. We conducted a double-blind, prospective, multicenter trial to compare ceftazidime with moxalactam in the treatment of serious gram-negative infections. The overall favorable response rates for the two regimens were similar (93 of 106 [88%] and 84 of 97 [86%], respectively). Among these, the response rates of the 56 gram-negative bacteremias and the 23 P. aeruginosa infections were comparable. Both groups had similar incidences of subsequent infections with P. aeruginosa, enterococci, and yeasts. A total of 13% of the patients in the moxalactam group developed a prolonged prothrombin time (P less than 0.01), and three patients demonstrated clinical bleeding. These results suggest that although the overall efficacy of both regimens was similar, treatment with moxalactam resulted in a higher incidence of prolongation of prothrombin time with an attendant risk of bleeding. In nonneutropenic patients, ceftazidime as a single agent is safe and effective in gram-negative bacillary infections.
Many infections are due to mixtures of facultative gram-negative bacilli and anaerobic bacteria. Moxalactam, a semisynthetic beta lactam antibiotic, is active against a wide range of anaerobic organisms, including most strains of Bacteroides fragilis, as well as many aerobic gram-negative bacilli. We performed a prospective, randomized controlled trial comparing moxalactam alone with the regimen of clindamycin and tobramycin for treatment of mixed aerobic/anaerobic infections. One hundred and six patients with presumed mixed infections were randomized to the study groups. The resultant groups were clinically and microbiologically comparable. The effectiveness of treatment was similar with both antibiotic regimens. Five of 25 patients tested in the moxalactam group had a prolongation of their prothrombin time and one of them developed clinically important bleeding. Two of the 23 patients tested in the clindamycin/tobramycin group had a prolonged prothrombin time with no bleeding. Decreases in hematocrit which could be "probably" or "possibly" related to antimicrobial use were seen in 6 of 48 moxalactam patients and none of 50 clindamycin/tobramycin patients (P = .03). Moxalactam, a potent antimicrobial for both anaerobic and aerobic organisms, demonstrated effectiveness in treating mixed anaerobic/aerobic infections similar to clindamycin/tobramycin but was associated with clinically important decreases in hematocrit.
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Lithium, a widely used substance for the treatment of manic-depressive illness, has been reported to alter the phase relationships of a variety of biological rhythms. We have previously found that lithium affects serum melatonin differently in albino compared to pigmented eye rats. The present study was undertaken to investigate the effect of lithium on pituitary rhythms in pigmented eye rats. Six point 24 hour maps were generated throughout a 12 hour light/12 hour dark lighting regime on separate groups of individually housed adult male Long Evans rats (with pigmented eyes), maintained for six weeks on ad lib water and either normal lab chow or lab chow supplemented with 50 mM/Kg of lithium chloride. Animals were sacrificed by rapid decapitation with care to ensure that blood samples were obtained from subjects in the resting, undisturbed state. Plasma lithium levels were 0.57 +/- 0.02 mEq/1. In comparison to normal controls, lithium treatment suppressed body weight by 19%, and increased water intake by 100%. Absolute corticosterone levels were not altered by lithium, but the 24-hour pattern was significantly changed. Growth hormone levels were significantly reduced by lithium treatment without alteration of the 24-hour pattern. Prolactin levels were significantly reduced by lithium and the normal 24-hour variation was attenuated. Comparison of these effects of lithium in pigmented eye rats with similar data from albino rats suggests that the effects on growth hormone, body weight and water intake were similar; however, the effects on prolactin and corticosterone differed.(ABSTRACT TRUNCATED AT 250 WORDS)
Following an open pilot study, BW 245C , a hydantoin prostaglandin analogue, was given by mouth in an aqueous solution to six healthy volunteers. The subjects received BW 245C 50 and 150 micrograms and placebo on separate occasions according to a double blind randomised design. Heart rate, blood pressure and, using visual analogue scales, facial flushing, abdominal discomfort and headache, were measured before dosing, at 15 minute intervals after dosing for 2 hours and at 30 minute intervals for a further 2 hours. Platelet aggregation responses to ADP and to collagen were measured before dosing and at 15 minutes, 45 minutes, 2 hours and 4 hours after dosing. Cutaneous bleeding time was measured before and 45 minutes after dosing. 150 micrograms BW 245C produced significant (p less than 0.05) facial flushing over the period from 15 to 120 minutes after dosing. Heart rate increased slightly but significantly (p less than 0.05) in response to both doses of 245C only at 75 minutes after dosing. Systolic and diastolic blood pressures were unchanged by either dose of BW 245C . Platelet aggregation responses to ADP were significantly (p less than 0.05) inhibited only at 120 minutes after 150 micrograms BW 245C . Aggregation responses to collagen were significantly (p less than 0.05) inhibited 45 and 120 minutes after 150 micrograms BW 245C and also at 120 minutes after 50 micrograms BW 245C . Bleeding time was unchanged in response to either dose of BW 245C . There was no change in headache or abdominal discomfort scores following either dose of BW 245C . Nausea was reported after 7 out of 12 administrations of BW245C but not after placebo. Nasal congestion was experienced by two subjects receiving 150 micrograms BW 245C and muscle tension and stiffness, especially of the jaw muscles, was also reported following administration of BW 245C but not of placebo. BW 245C is active when given by mouth and has similar pharmacodynamic effects to prostacyclin in man.
Lithium has been suggested to exert some of its theraputic effects by modifying the function of the retinal-hypothalamic pineal pathway that is essential for the chronobiology of an organism (Seggie et al., 1983). Previous work was done in Wistar rats, an Albino species which lacks the enzyme for synthesis of eye pigment. This pigment is important in the regulation of light cued rhythms. The present project investigated effects of lithium in a pigmented eye strain. Adult male Long Evans rats were maintained individually on a 12 hour light/12 hour dark schedule with free access to water and one of three diets: (1) normal laboratory chow; (2) a low lithium diet: lab chow supplemented with 50 mM/kg of lithium chloride. Body weight and water intake were measured after six weeks on the diets. In Experiment I, separate groups of rats were sacrificed by rapid decapitation every 4 hours in the light/dark cycle. In Experiment II, animals were sacrificed every 90 min. between 12:00 and 20:00 hours during the dark cycle. Blood and pineal glands were collected for lithium determination and assay of melatonin by RIA. In Experiment I, plasma lithium levels were 0.35 +/- 0.01 and 0.57 +/- 0.02 mEq/1 for the low and high diets. Serum and pineal melatonin evidenced the expected diurnal rhythms. The diets had no effect on these parameters except at 14:00 hours.(ABSTRACT TRUNCATED AT 250 WORDS)
Lithium has been implicated in chronobiology (Seggie, et al., 1982, 1983). Previous work was done in Wistar rats, an Albino species, which lack the enzyme for synthesis of eye pigment. This pigment is important in regulation of light cued rhythms. The present project extends observations to Long Evans rats, a strain which has a pigmented eye. Groups of adult male rats were fed one of three diets: (1) normal laboratory chow; (2) a low lithium diet: lab chow supplemented with 30 mM/kg lithium chloride; and (3) a high lithium diet: lab chow supplemented with 50 mM/kg lithium chloride. Adult male rats were house individually with free access to diet and water under a 12 hour light/12 hour dark schedule. After six weeks on the diets, body weight, water intake, plasma, red blood cell and retinal lithium and retinal weight were measured every 4 hours throughout the 24 hour cycle following sacrifice by rapid decapitation. Plasma lithium levels on the high diet were 0.57 +/- 0.02 mEq/l and did not evidence a diurnal rhythm. Plasma lithium levels on the low diet were 0.35 +/- 0.01 mEq/l and evidenced a small, but significant diurnal rhythm with levels lowest just before darkness and normal food intake. Red blood cell lithium levels were significantly higher than plasma levels at 0.83 +/- 0.02 and 0.52 +/- 0.02 mEq/l for the high and low diets. Low diet, but not high diet red blood cells lithium levels evidenced a significant rhythm with a pattern similar to that seen in plasma lithium levels.(ABSTRACT TRUNCATED AT 250 WORDS)
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